Experimental Therapeutics is the programmatic home for basic and clinical investigators involved in a broad spectrum of studies in cancer therapeutics. The goals of the program are: (1) to develop novel agents for the treatment of cancer based upon targets identified in this and other programs, (2) to improve the activities of established classes of drugs by structural modification and/or enhanced understanding of their pharmacological properties, (3) to develop more effective clinical therapeutic regimens within the context of disease-focused working groups. Preclinical drug development continues in the areas of transition-state inhibitors, novel microtubule-stabilizing agents, and a diverse spectrum of immunotherapeutics. Two transition-state inhibitors are now in clinical trials, one advanced. A third is moving forward to the clinic. A monoclonal antibody (moab) to melanin linked to 188-rhenium completed Phase I clinical trials for the treatment of advanced melanoma. Other moab-radionuclides are being developed targeting cervical and pancreatic cancers. An agent for the prevention of the dermatitis due to EGFR inhibitors recently entered a Phase II clinical trial. The spectrum of agents studied has broadened to encompassing aptamers, high-affinity antibodies, agents to block apoptotic pathways or targeted to surface glycans. Research in biologicals is focused on co-inhibitory elements within the immune synapse with the objective of developing agents that modulate tolerance, research activities supported by the expanding capabilities in protein production, synthetic chemistry, x-ray crystallography, NMR, and mass spectroscopy with bioinformatics and systems and computational biology support. Disease-focused working groups encompassing basic and clinical investigators have been expanded in breast, gynecological, lung, and head/neck cancers and in the hematological malignancies. Neuro-oncology and neuroendocrine tumors groups were recently formed. Recruitment of clinical and translational researchers has been enhanced by a recently funded Paul Calabresi Career Development Award for Clinical Oncology Scholars. Access to patients for clinical trials has been enhanced at the affiliated Montefiore Medical Center by the creation of the multidisciplinary Montefiore-Einstein Center for Cancer Care and the recruitment of a cadre of clinician investigators. AECC members play important roles in ECOG-ATRIN, GOG, COG, and the AIDS Malignancy Consortium. There are currently 54 members from 23 departments, supported by 10 NCI grants ($2.6M Direct) and 21 other peer-reviewed cancer-relevant grants ($10.2M Direct). Since the last CCSG review there have been 537 cancer-relevant research papers by members of this program of which 29% represent intraprogrammatic, and 27% represent interprogrammatic publications.